However, despite its widespread use (6, 9, 10, 20, 25, 29), the DLW method has some major limitations. Individual measurements are only precise to ± 7 % at best (23), so the method is currently most suitable for studies of groups rather than individual variation. A second problem is that the test is expensive to perform due to the need for relatively large sample sizes to achieve sufficient statistical power, the large quantities of H218O needed for dosing (23), and IRMS analysis. High levels of 18O are required to distinguish the dose from background isotope levels after 10 - 21 days of elimination. It currently costs $500 - $750 for the 18O required to perform a DLW measurement on an adult subject (50 - 75 kg fat free mass) and the cost is unpredictable due to fluctuations in demand from the medical diagnostic PET scan. The need for high 18O enrichments is caused by fluctuations in the background isotope levels over time (8). This uncertainty in the background levels increases the isotope dose that must be administered and contributes to the uncertainty in the DLW measurements as compared to the reference calorimetry measurements of TEE in validation studies. Finally, IRMS analysis presents its own set of challenges, including the need for sophisticated, expensive instrumentation with dedicated, highly trained operators, and, in general, measurement of only one isotope ratio at a time, reducing analytical throughput. Because of these challenges, most researchers conducting DLW tests do not maintain in-house IRMS facilities, relying instead on expensive and slow analyses by outside measurement laboratories. The proposed work will address these problems by developing a new triple-isotope method for DLW analysis, significantly improving the individual accuracy of the measurements and reducing the cost of the DLW method, leading to more widespread use of the DLW method in both clinical and research applications.